Researchers work to defeat acne by understanding it better on a molecular level

Sep 2 2004

To defeat an enemy, you must first understand it, or so the saying goes. And for nearly every teenager and young adult, acne is a formidable foe, causing damage to their skin and their self-image that can leave long-lasting physical and emotional scars.

But University of Michigan researchers are working to defeat acne by understanding it better on a molecular level, and testing new ideas about how to treat it. They’ve enlisted armies of volunteers in their efforts to explore acne’s roots in the cells and chemicals under the surface of the skin, and to try new combinations of pills, creams and other potential therapies. And they need more recruits to continue the fight.

The U-M research builds on what’s already known about acne from years of study. And new science is also helping to dispel old myths about what causes the most common skin condition in the country. Acne affects about 80 percent of people between the ages of 11 and 30, some 40 to 50 million individuals.

Sewon Kang, M.D., the dermatologist who helps lead the U-M Health System’s acne research and other skin studies, notes that acne is still a mysterious enemy.

“The cause of acne still remains unknown, but what we do know about it is that when you look at the types of spots that make up acne, in the plugged pores or pimples and the red bumps, there seems to be involvement of what we call inflammatory cells,” he says. “And there seems to be an increase in the oil production in the skin, which patients often feel on their skin.” Bacteria called Propionibacterium acnes also appear to play a role, thriving in the tiny pits, or follicles, where acne pimples start.

Stress may also be a factor in acne, says Kang. “We often find college students around the time of midterms and final exam period have more problems with acne flare-ups,” he says. Since science is increasingly proving that mental stress can produce physical effects throughout the body, the connection seems plausible, he adds.

Hormone changes, like the ones that come with puberty and with a woman’s menstrual cycle, also act as acne triggers.

But one thing that researchers agree doesn’t cause acne is poor hygiene — getting pimples has nothing to do with being “dirty.”

They’re also skeptical of claims that certain foods — chocolate, pizza, french fries — can trigger acne, though Kang notes it can’t hurt for individuals to avoid foods they associate with their pimples.

To get at the root cause of acne, research in the U-M Department of Dermatology looks at inflammation on a sub-microscopic level, studying the molecules that attract the inflammatory cells that make the skin red and bumpy. Kang and his colleagues also probe the effect that acne has on the skin’s inner structure and repair mechanisms.

Depending on how severe a person’s acne is, the damage done during a flare-up can overwhelm the skin’s ability to heal itself. And the inflammation itself attracts molecules that break down the collagen that makes skin firm and smooth. In severe cases, the result can be scars that give the skin a pitted look for the rest of a person’s life.

“Acne certainly is not a life-threatening condition, but it isn’t a trivial issue either,” says Kang. “It usually begins around puberty, when a lot of people already have a tough time dealing with changes in themselves and at school or home. And for those with the severe form of acne, you can get permanent disfigurement that will remain with the person even after the active spots have gone away. This can have significant psycho-social impact on a person’s well-being.”

To reduce or prevent this long-term mental and physical harm, Kang and his colleagues recommend aggressive treatment of severe acne with the therapies that have been proven to work.

The drug sold as Accutane (isotretinoin) is the best for severe cases, he notes, but it shouldn’t be taken lightly. It can cause severe birth defects, so any young woman of childbearing age must be using two forms of birth control while she is on Accutane, and receive regular pregnancy tests. And the mental health of people on Accutane must be monitored; a firm link has not been established between the drug and depression, but there’s enough concern to warrant caution, Kang says.

“For individuals with what we call nodulocystic acne, which causes inflamed large lumps on the face that lead to scarring, Accutane can be a great drug,” he says. “But we use it in a very careful manner so that we don’t run into difficulties.”

The active ingredient in Accutane is a cousin to vitamin A, and other molecules in this family can help less severe acne when used in a topical cream, such as tretinoin (Retin-A). So can antibiotics, either in cream form or in pill form — these help control the P. acnes bacteria inside inflamed follicles. And, U-M research has shown that birth control pills can be used in combination with topical agents to reduce acne further, though they don’t seem to work well on their own.

But there are also therapies out there that don’t work against acne and its scars, despite claims to the contrary by their makers, says Kang, a professor of dermatology at the U-M Medical School. He directs the Clinical Pharmacology Unit where volunteers with acne can enroll in scientific studies of new treatments, and he notes that studies of acne therapies and other skin treatments aren’t always done in a way that can give solid proof that the technique works.

For example, pulsed-dye laser therapy has been touted as an acne cure. But a U-M team recently reported the results of a study which indicates that it isn’t. They used pulsed-dye laser therapy on one half of 40 participants’ acne-studded faces, and no laser on the other half of their faces. Over several months of observation, there was no major difference in the acne two sides of the faces.

Kang notes that other researchers had reported that the pulsed-dye laser had worked in acne patients, but their study only included people who either had or hadn’t received laser therapy on their whole face. Because the U-M study compared two sides of a single person’s face, the results give a better indication of the therapy’s effectiveness. The U-M study was published in the Journal of the American Medical Association in June.

It remains to be seen whether other light-based therapy, including other laser techniques, might help with acne and scarring, says Kang.

The U-M team is now seeking participants for a range of studies on new options for acne treatment, including therapies that try to reduce the immune system’s response to acne pimples, and thereby calm the inflammation.

“By treating inflammation, we hope we can make an impact in scar prevention,” says Kang. “We’re focusing on trying different agents that might be effective down the road, and we’re still looking for volunteers who might be interested in working with us on this project.”

As the war against acne continues, Kang adds, more knowledge of what acne is and what it does under the skin will help win battles, one patient at a time.

For more information about acne studies at the Clinical Pharmacology Unit of the U-M Department of Dermatology, call (734) 936-4070.

Facts about acne and its treatment:

• About 80 percent of teens and young adults between the ages of 11 and 30 have acne.
• Acne is the most common skin condition in the country, affecting up to 50 million people.
• The exact cause of acne is unknown, but it involves the inflammatory cells of the body’s immune system, bacteria called P. acnes, and excess oil production in the skin. Stress and hormone changes appear to trigger flare-ups, but poor hygiene and foods do not.
• Acne symptoms include whiteheads, which result from plugged oil glands in the skin; blackheads, which are whiteheads that have been exposed to air; and pustules, which are red, inflamed, infected oil glands. In severe cases, cysts (fluid-filled bumps) can develop.
• Acne can form on the face, neck, back and other areas. Each acne lesion (pimple) begins in a follicle, or tiny pit in the skin at the base of a hair. Bacteria in the follicle and molecules that attract immune system components cause inflammation.
• Severe acne can cause permanent scarring, if the skin’s repair mechanism can’t keep up with the damage done during a flare-up. Scarring can have long-term psychological effects.
• There are effective treatments for mild to severe acne, from antibiotic creams and pills to Accutane. But pills and creams must be used regularly to prevent repeated flare-ups, and Accutane carries risks of birth defects and possible mental health effects.
• Molecular research is revealing how acne occurs, and how it might be stopped. Meanwhile, scientific studies are needed to find out whether treatments like lasers live up to their claims.
• New approaches may be based on dampening the immune system’s response to pimples, which could reduce inflammation and scarring.

For more information on acne:

https://www.news-medical.net/?keyword=Acne

http://www.med.umich.edu/1libr/aha/aha_acne_crs.htm

http://www.derm-infonet.com/acnenet/acne.html